1. Field of the Invention
The present invention relates to the field of mass spectrometry, and more particularly to a mass spectrometer system and intra-scan method for increasing the measured peak resolution at different regions of a given mass spectrum while not significantly increasing the total duration of the scan.
2. Discussion of the Related Art
Data-dependent acquisition involves using data derived from an experimentally-acquired mass spectrum in an “on-the-fly” manner to direct the subsequent operation of a mass spectrometer; for example, a mass spectrometer may be switched between MS and MS/MS scan modes upon detection of an ion species of potential interest. Utilization of data-dependent acquisition methods in a mass spectrometer provides the ability to make automated, real-time decisions in order to maximize the useful information content of the acquired data. Current systems and methods that provide for real time data dependent functionality include, but are not limited to: the Data Dependent Experiment™ (DDE) tool utilized by Thermo Finnigan LLC of San Jose, Calif., the Data Directed Analysis (DDA) tool by Waters Corporation (Micromass™) and the Information Dependant Acquisition™ (IDA™) system marketed by MDS Sciex Inc. and Applera Corporation.
Data-dependent acquisition methods may be characterized as having one or more input criteria, and one or more output actions. The input criteria employed for conventional data-dependent methods are generally based on parameters such as intensity, intensity pattern, mass window, mass difference (neutral loss), mass-to-charge (m/z) inclusion and exclusion lists, and product ion mass. The input criteria are employed to select one or more ion species that satisfy the criteria. The selected ion species are then subjected to an output action (examples of which include performing MS/MS or MSn analysis and/or high-resolution scanning). In one instance of a typical data-dependent experiment, a group of ions are mass analyzed, and precursor ion species having mass spectral intensities exceeding a specified threshold are subsequently selected as precursor ions for MS/MS analysis, which may involve operations of isolation, dissociation (i.e., fragmentation) of the precursor ions, and mass analysis of the product ions.
Generally, a mass spectrometer configured to provide such operations most often includes: an ion source to transform introduced molecules in a sample into ionized fragments; an analyzer to separate such ionized ions by their masses by applying electric and magnetic fields; and a detector to measure and thus provide data for identifying and calculating the abundances of each ion fragment present. Moreover, such a mass spectrometer system often can and does include a two-dimensional (2D) and/or a three-dimensional (3D) ion trap that enables the forming and storage of ions over a large range of masses for relatively large periods of time. Eventually, the interrogation of the contents of such ion traps is necessary, which may require different scanning implementations at designed scanning rates so as to provide a given resolution.
However, a constraint that has continued to limit the capabilities of such 2D and 3D ion trap instruments is that different regions of a scanned resultant mass spectrum often requires different resolutions to obtain the analytical objectives of the experiment. As an illustration, a commercial ion trap (e.g., an LTQ linear ion trap spectrometer from Thermo Fisher Scientific) scanned at a fixed rate of 16,666 Da/Sec may be preferably selected as a rate of choice based on the desire to achieve unit mass resolution but unit resolution may not prove sufficient in selected regions of the mass spectrum. One way of overcoming such a problem includes, but is not limited to, reducing the scanning rate across the entire desired mass spectrum.
Still, while reducing the scan rate is an effective way to improve the mass resolution, the time it takes to scan between masses can often involve a significant time increase, which can among other problems present practical problems in terms of the length of the experiment and can add complications with respect to system electronics that require stabilization time periods and/or that may drift and induce deleterious mass axis instabilities.
Background information on a mass filter system that alternates between a fast scan (i.e., measurement scan) and a slow scan (i.e., a survey scan) based on a pre-scan map, is described and claimed in U.S. Pat. No. 4,837,434, entitled, “Mass Spectrometry System And Method Employing Measurement/Survey Scan Strategy,” issued Jun. 6, 1989, to James, including the following, “A gas chromatography plus mass spectrometry system implements a scan strategy in which each full range scan alternates between a normal measurement mode and a survey mode based on a block/gap map made during the previous scan. Survey mode is used within regions that were determined in the previous scan to lack signal above a predetermined threshold. Spectral data is generated during measurement mode operation. Each scan serves both measurement and mapping functions in a way that avoids mass filter jumps, since each scan is monotonic over the entire scanning range.”
Background information for a system that provides for high mass resolution scanning of an ion trap's contents, is described and claimed in U.S. Pat. No. 5,397,894, entitled, “Method Of High resolution Scanning Of An Ion Trap Mass Spectrometer,” issued Mar. 14, 1995, to Wells et al., including the following, “A method of using a quadrupole ion trap mass spectrometer for high resolution mass spectroscopy is disclosed. High resolution of a mass spectrum of a desired species is achieved by first using a slow scanning rate and by first ridding the trap of unwanted ions. Accurate mass calibration is achieved by using a reference compound of known mass and using a second supplemental AC dipole voltage to eject the reference ions at nearly the same time as the sample ions of interest are ejected from the trap. This eliminates the need to scan the trap between the between the masses of the sample and reference ions . . . ”
Accordingly, a need exists for a mass spectrometer system that utilizes an intra-scan method of providing different resolutions to desired regions of a mass spectrum without significantly increasing the duration of the scan. The present invention is thus directed to such a need.